---
title: "BMP2/4 signaling rewires glioma cell death responses in high-throughput spheroid profiling"
id: "biorxiv-22-high-throughput-spheroid-profiling-reveals-bmp-driven-rewiring-of-glioma-cell"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-22-high-throughput-spheroid-profiling-reveals-bmp-driven-rewiring-of-glioma-cell"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.10.750657v1?rss=1"
published_at: "2026-09-13T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# BMP2/4 signaling rewires glioma cell death responses in high-throughput spheroid profiling
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-22-high-throughput-spheroid-profiling-reveals-bmp-driven-rewiring-of-glioma-cell
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.10.750657v1?rss=1)
- **Published At:** 2026-09-13T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The authors developed a **high-throughput spheroid** assay to study cell death in patient-derived glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) models grown as spheroids. - They systematically profiled how extracellular ligands change sensitivity to compound-induced cell death across these spheroid models. - **Bone morphogenetic proteins (BMP2 and BMP4)** were identified as potent modulators that rewire cell death responses. - BMP2/4 suppressed killing by standard-of-care **DNA alkylating agents** and by **kinase inhibitors**, an effect attributed to inhibition of cell cycle progression. - Concurrently, BMP2/4 primed spheroids for a form of non-apoptotic, **lipid-dependent necrosis (LiDN)** that requires palmitate and can be triggered by the clinical drug candidate **tegavivint**. - Activating mutations in the **BMP receptor ACVR1**, present in about ~25% of DIPG tumors, were sufficient to prime cells for LiDN without exogenous BMP ligand. - The findings describe a switch in cell death modality in glioma cells driven by BMP signaling, with potential implications for therapeutic response and for exploiting LiDN induction as a therapeutic strategy. - The source reports these core results but does not present comprehensive clinical translation data, in vivo efficacy, or detailed mechanistic biochemical timelines beyond the summarized links between BMP signaling, cell cycle inhibition, and LiDN priming.
## Clinical Analysis & Structured Key Points
High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses | bioRxiv Skip to main content New Results High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses Weaverly Colleen Lee , Jennifer J. Salinas , Aastha Gautam , Dimitri Cadet , Matei A. Banu , David A. Nathanson , View ORCID Profile Scott J Dixon doi: https://doi.org/10.64898/2026.09.10.750657 Weaverly Colleen Lee 1 Stanford University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jennifer J. Salinas 2 UCLA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Aastha Gautam 1 Stanford University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Dimitri Cadet 2 UCLA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matei A. Banu 1 Stanford University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site David A. Nathanson 2 UCLA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Scott J Dixon 1 Stanford University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Scott J Dixon For correspondence: sjdixon{at}stanford.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract The mechanisms regulating glioma cell death are poorly understood. Here, we developed a high-throughput method to study cell death in patient-derived glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) spheroids. Using this method, we systematically profiled how extracellular ligands modulate compound-induced cell death. We find that bone morphogenetic protein 2 (BMP2) and BMP4 potently rewire cell death sensitivity. These ligands suppress killing by standard-of-care DNA alkylating agents and kinase inhibitors by inhibiting cell cycle progression. Simultaneously, BMP2/4 prime spheroids for lipid-dependent necrosis (LiDN), a palmitate-dependent form of non-apoptotic cell death that can be triggered by the clinical drug candidate tegavivint. Activating mutations in the BMP receptor ACVR1, found in ~25% of DIPG tumors, are sufficient to prime cells for LiDN in the absence of BMP ligand. Together, these findings identify a cell death switch that can be activated in glioma cells by BMP signaling. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Charlie Teo Foundation National Institutes of Health, https://ror.org/01cwqze88 , R01NS143119 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted September 13, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses Weaverly Colleen Lee , Jennifer J. Salinas , Aastha Gautam , Dimitri Cadet , Matei A. Banu , David A. Nathanson , Scott J Dixon bioRxiv 2026.09.10.750657; doi: https://doi.org/10.64898/2026.09.10.750657 Share This Article: Copy Citation Tools High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses Weaverly Colleen Lee , Jennifer J. Salinas , Aastha Gautam , Dimitri Cadet , Matei A. Banu , David A. Nathanson , Scott J Dixon bioRxiv 2026.09.10.750657; doi: https://doi.org/10.64898/2026.09.10.750657 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (7982) Biochemistry (18684) Bioengineering (14804) Bioinformatics (44277) Biophysics (22531) Cancer Biology (19650) Cell Biology (26810) Clinical Trials (138) Developmental Biology (13915) Ecology (20940) Epidemiology (2067) Evolutionary Biology (25400) Genetics (16131) Genomics (23441) Immunology (18640) Microbiology (42360) Molecular Biology (17992) Neuroscience (93155) Paleontology (695) Pathology (2974) Pharmacology and Toxicology (5075) Physiology (8087) Plant Biology (15944) Scientific Communication and Education (2094) Synthetic Biology (4546) Systems Biology (10201) Zoology (2381)
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